Thyroid nodules are common in the United States, occurring in greater than 60% of individuals. Moreover, their incidence is steadily increasing, mainly because of the increased detection of smaller, asymptomatic nodules. Although the majority of these nodules are benign, a significant numbers of patients undergo surgical excision. Upon pathologic review of such thyroid tumors, clear-cut benign or malignant diagnoses often can be rendered. However, follicular lesions of the thyroid often pose a diagnostic challenge.
A particular diagnostic dilemma is presented in a subset of encapsulated follicular lesions with partial nuclear features of papillary thyroid carcinoma (PTC) (occasional nuclear grooves, focal nuclear clearing, and overlapping nuclei) and with histological features that fail to place them reliably in either the benign category or the malignant category. In the inventors' experience, these tumors represent approximately 10% of all follicular-patterned lesions observed at surgical pathology (see also, Arora et al. World J Surg. 32:1237-1246 (2008)). The difficulty of classifying this group of tumors is exemplified further by several studies in which poor inter-observer agreement was demonstrated among expert endocrine pathologists ranging from 39% to 58% when they reviewed follicular-patterned lesions of the thyroid (Chan et al., Am J Clin Pathol. 117:16-18 (2002); Franc et al., Hum Pathol. 34:1092-1100 (2003); Lloyd et al., Am J Surg Pathol. 28:1336-1340 (2004); Saxen et al. Acta Pathol Microbiol Scand [A]. 1978; 86A:483-4864-8 (1978); Hirokawa et al. Am J Surg Pathol. 26:1508-1514 (2002)). This diagnostic difficulty in classifying such borderline tumors with standard terminology led Williams to propose the term well differentiated tumor of uncertain malignant potential (WDT-UMP) as a separate diagnostic category (Int J Surg Pathol. 8:181-183 (2000).
No matter what terminology is used for these tumors, additional tools are needed to determine whether thyroid nodules and/or tumors are actually malignant or simply benign, and/or whether such nodules and/or tumors can progress to become malignant tumors.